scholarly journals The Lacto-Tetrapeptide Gly–Thr–Trp–Tyr, β-Lactolin, Improves Spatial Memory Functions via Dopamine Release and D1 Receptor Activation in the Hippocampus

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2469 ◽  
Author(s):  
Tatsuhiro Ayabe ◽  
Yasuhisa Ano ◽  
Rena Ohya ◽  
Shiho Kitaoka ◽  
Tomoyuki Furuyashiki

Scope: Peptides containing tryptophan–tyrosine sequences, including the lacto-tetrapeptide glycine–threonine–tryptophan–tyrosine (GTWY) and β-lactolin, from β-lactoglobulin in whey enzymatic digestion, enhance hippocampus-dependent memory functions, which are blocked by the systemic administration of dopamine D1-like antagonist. In this study, we investigated the role of the hippocampal dopaminergic system in the memory-enhancing effect of β-lactolin. Methods and Results: The results of in vivo microdialysis revealed that oral administration of β-lactolin increased the extracellular concentration of dopamine in the hippocampus and enhanced both spatial working memory, as measured in the Y-maze test, and spatial reference memory, as measured in the novel object location test. These memory-enhancing effects of β-lactolin, but not the baseline memory functions, were impaired by the knockdown of the dopamine D1 receptor subtype in the hippocampus. β-Lactolin also enhanced object memory, as measured by the novel object recognition test. However, D1 knockdown in the hippocampus spared this memory function either with or without the administration of β-lactolin. Conclusions: The present results indicate that oral administration of β-lactolin increases dopamine release and D1 receptor signaling in the hippocampus, thereby enhancing spatial memory, but it may improve object memory via a separate mechanism.

2020 ◽  
Vol 14 (2) ◽  
pp. 220-233 ◽  
Author(s):  
Noritaka Nakamichi ◽  
Shunsuke Nakao ◽  
Misa Nishiyama ◽  
Yuka Takeda ◽  
Takahiro Ishimoto ◽  
...  

Background: The enhancement of learning and memory through food-derived ingredients is of great interest to healthy individuals as well as those with diseases. Ergothioneine (ERGO) is a hydrophilic antioxidant highly contained in edible golden oyster mushrooms (Pleurotus cornucopiae var. citrinopileatus), and systemically absorbed by its specific transporter, carnitine/organic cation transporter OCTN1/SLC22A4. Objective: This study aims to examine the possible enhancement of object recognition memory by oral administration of ERGO in normal mice. Method: Novel object recognition test, spatial recognition test, LC-MS/MS, Golgi staining, neuronal culture, western blotting, immunocytochemistry, and quantitative RT-PCR were utilized. Result: After oral administration of ERGO (at a dose of 1–50 mg/kg) three times per week for two weeks in ICR mice, the novel object recognition test revealed a longer exploration time for the novel object than for the familiar object. Oral administration of ERGO also revealed a longer exploration time for the moved object in the spatial recognition test in mice fed ERGO-free diet. The discrimination index was significantly higher in the ERGO-treated group than the control in both behavioral tests. ERGO administration led to an increase in its concentration in the plasma and hippocampus. The systemic concentration reached was relevant to those found in humans after oral ERGO administration. Golgi staining revealed that ERGO administration increased the number of matured spines in the hippocampus. Exposure of cultured hippocampal neurons to ERGO elevated the expression of the synapse formation marker, synapsin I. This elevation of synapsin I was inhibited by the tropomyosin receptor kinase inhibitor, K252a. Treatment with ERGO also increased the expression of neurotrophin-3 and -5, and phosphorylated mammalian target of rapamycin in hippocampal neurons. Conclusion: Oral intake of ERGO which provides its plasma concentration achievable in humans may enhance object recognition memory, and this enhancement effect could occur, at least in part, through the promotion of neuronal maturation in the hippocampus.


Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7168
Author(s):  
Haya Hussain ◽  
Shujaat Ahmad ◽  
Syed Wadood Ali Shah ◽  
Mehreen Ghias ◽  
Abid Ullah ◽  
...  

Cognitive decline in dementia is associated with deficiency of the cholinergic system. In this study, five mono-carbonyl curcumin analogs were synthesized, and on the basis of their promising in vitro anticholinesterase activities, they were further investigated for in vivo neuroprotective and memory enhancing effects in scopolamine-induced amnesia using elevated plus maze (EPM) and novel object recognition (NOR) behavioral mice models. The effects of the synthesized compounds on the cholinergic system involvement in the brain hippocampus and their binding mode in the active site of cholinesterases were also determined. Compound h2 (p < 0.001) and h3 (p < 0.001) significantly inhibited the cholinesterases and reversed the effects of scopolamine by significantly reducing TLT (p < 0.001) in EPM, while (p < 0.001) increased the time exploring the novel object. The % discrimination index (DI) was significantly increased (p < 0.001) in the novel object recognition test. The mechanism of cholinesterase inhibition was further validated through molecular docking study using MOE software. The results obtained from the in vitro, in vivo and ex vivo studies showed that the synthesized curcumin analogs exhibited significantly higher memory-enhancing potential, and h3 could be an effective neuroprotective agent. However, more study is suggested to explore its exact mechanism of action.


2021 ◽  
Author(s):  
◽  
Miriam Collins

<p>Previous research has demonstrated that ethanol produces differential effects on non-spatial or recognition memory and spatial memory; spatial memory deficits were consistently found to be more persistent than non-spatial memory deficits. Ethanol-produced deficits have also been found to be dependent on age at exposure, and exposure during adolescence produced more persistent deficits than when exposure was experienced by older subjects.  The current study investigated the effects of a “binge-like’ 5 day episode of ethanol exposure (1.0g/kg x 5) on performance in non-spatial and spatial forms of the novel object recognition (NOR) task. Subjects were exposed either during adolescence or following maturity. Tests were conducted 2 or 9 days following exposure. NOR was tested following inter-trial intervals of 1, 3, or 5 minutes. Data from mature rats could not be obtained or analysed due to procedural issues that precluded NOR measurement. Control rats failed to demonstrate NOR at any of the time intervals. Reasons for these negative findings are discussed.</p>


2017 ◽  
Vol 13 (7) ◽  
pp. 20170183 ◽  
Author(s):  
Trevor J. Hamilton ◽  
Martin Tresguerres ◽  
David I. Kline

Object recognition memory is the ability to identify previously seen objects and is an adaptive mechanism that increases survival for many species throughout the animal kingdom. Previously believed to be possessed by only the highest order mammals, it is now becoming clear that fish are also capable of this type of memory formation. Similar to the mammalian hippocampus, the dorsolateral pallium regulates distinct memory processes and is modulated by neurotransmitters such as dopamine. Caribbean bicolour damselfish ( Stegastes partitus ) live in complex environments dominated by coral reef structures and thus likely possess many types of complex memory abilities including object recognition. This study used a novel object recognition test in which fish were first presented two identical objects, then after a retention interval of 10 min with no objects, the fish were presented with a novel object and one of the objects they had previously encountered in the first trial. We demonstrate that the dopamine D 1 -receptor agonist (SKF 38393) induces the formation of object recognition memories in these fish. Thus, our results suggest that dopamine-receptor mediated enhancement of spatial memory formation in fish represents an evolutionarily conserved mechanism in vertebrates.


2021 ◽  
Author(s):  
◽  
Miriam Collins

<p>Previous research has demonstrated that ethanol produces differential effects on non-spatial or recognition memory and spatial memory; spatial memory deficits were consistently found to be more persistent than non-spatial memory deficits. Ethanol-produced deficits have also been found to be dependent on age at exposure, and exposure during adolescence produced more persistent deficits than when exposure was experienced by older subjects.  The current study investigated the effects of a “binge-like’ 5 day episode of ethanol exposure (1.0g/kg x 5) on performance in non-spatial and spatial forms of the novel object recognition (NOR) task. Subjects were exposed either during adolescence or following maturity. Tests were conducted 2 or 9 days following exposure. NOR was tested following inter-trial intervals of 1, 3, or 5 minutes. Data from mature rats could not be obtained or analysed due to procedural issues that precluded NOR measurement. Control rats failed to demonstrate NOR at any of the time intervals. Reasons for these negative findings are discussed.</p>


2013 ◽  
Vol 552 ◽  
pp. 5-9 ◽  
Author(s):  
Alfonso Alfaro-Rodriguez ◽  
María Alonso-Spilsbury ◽  
Emilio Arch-Tirado ◽  
Rigoberto Gonzalez-Pina ◽  
José-Antonio Arias-Montaño ◽  
...  

1992 ◽  
Vol 267 (25) ◽  
pp. 17780-17786
Author(s):  
N.J. Pollock ◽  
A.M. Manelli ◽  
C.W. Hutchins ◽  
M.E. Steffey ◽  
R.G. MacKenzie ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 465
Author(s):  
Silvia Cerantola ◽  
Valentina Caputi ◽  
Gabriella Contarini ◽  
Maddalena Mereu ◽  
Antonella Bertazzo ◽  
...  

Antidopaminergic gastrointestinal prokinetics are indeed commonly used to treat gastrointestinal motility disorders, although the precise role of dopaminergic transmission in the gut is still unclear. Since dopamine transporter (DAT) is involved in several brain disorders by modulating extracellular dopamine in the central nervous system, this study evaluated the impact of DAT genetic reduction on the morpho-functional integrity of mouse small intestine enteric nervous system (ENS). In DAT heterozygous (DAT+/−) and wild-type (DAT+/+) mice (14 ± 2 weeks) alterations in small intestinal contractility were evaluated by isometrical assessment of neuromuscular responses to receptor and non-receptor-mediated stimuli. Changes in ENS integrity were studied by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (). DAT genetic reduction resulted in a significant increase in dopamine-mediated effects, primarily via D1 receptor activation, as well as in reduced cholinergic response, sustained by tachykininergic and glutamatergic neurotransmission via NMDA receptors. These functional anomalies were associated to architectural changes in the neurochemical coding and S100β immunoreactivity in small intestine myenteric plexus. Our study provides evidence that genetic-driven DAT defective activity determines anomalies in ENS architecture and neurochemical coding together with ileal dysmotility, highlighting the involvement of dopaminergic system in gut disorders, often associated to neurological conditions.


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